The investigators propose to study the relationship between ambient air pollution and birth defects in the five-county metropolitan Atlanta area, 1968-2002. A growing body of evidence suggests urban air pollution may influence reproductive outcomes. In a recent study based in Los Angeles, Ritz and colleagues (2002) reported an association of certain cardiac birth defects with ambient air pollution levels estimated to have occurred during the second month of gestation, a period when the heart is developing. The proposers seek to replicate and extend this work in a new study based in Atlanta, a city with relatively high ambient pollutant levels. The study will take advantage of the availability of a rich database on ambient air quality and one of the oldest birth defects surveillance systems in the U.S. with active case ascertainment. For the 35-year study period, the proposers will obtain data on air pollution levels from the state monitoring network and several intensive air quality studies, data on birth defects from the Metropolitan Atlanta Congenital Defects Program (MACDP) operated by CDC, and data on the underlying cohort of births and fetal deaths from the Georgia Division of Public Health Vital Records. The investigators will perform temporal analyses for the period 1968-2002, and spatio-temporal analyses for the period 1980-2002, when individual-level data are available on births and fetal deaths. The primary study hypotheses relate to the specific associations reported by Ritz et al. (2002): second gestational month carbon monoxide levels and ventricular septal defects, and second month ozone levels with three other cardiac anomalies. The study will include over a million births, 38,000 birth defects, and 10,000 cardiac defects. The study will have excellent power to assess the study hypotheses, with over 99% power to observe effect sizes similar to those reported by Ritz et al. (2002), and 80% power to detect substantially smaller effects. A second major study contribution involves updating the cardiac defects classification system used by the MACDP to incorporate current embryological knowledge. The study will entail close collaboration among investigators at Emory, Georgia Tech, and CDC, capitalizing on the team's experience with the MACDP and studies of air pollution in Atlanta.